In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues

Lyndsay E.A. Young, Lindsey R. Conroy, Harrison A. Clarke, Tara R. Hawkinson, Kayli E. Bolton, William C. Sanders, Josephine E. Chang, Madison B. Webb, Warren J. Alilain, Craig W. Vander Kooi, Richard R. Drake, Douglas A. Andres, Tom C. Badgett, Lars M. Wagner, Derek B. Allison, Ramon C. Sun, Matthew S. Gentry

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix-assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma.

Original languageEnglish
Article numbere16029
JournalEMBO Molecular Medicine
Volume14
Issue number11
DOIs
StatePublished - Nov 8 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords

  • Ewing sarcoma
  • MALDI imaging
  • glycogen
  • glycogen storage disease
  • spatial metabolism

ASJC Scopus subject areas

  • Molecular Medicine

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